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Abstract Background Eosinophils are involved in various inflammatory processes including allergic inflammation during which angiogenesis has been documented. Angiogenesis is most likely connected to the hypoxia which characterizes inflamed tissues. Eosinophils produce VEGF and are pro-angiogenic. However, to the best of our knowledge no study has been performed to verify the existence of a direct link between eosinophils, hypoxia and angiogenesis in allergic inflammation. Objective To characterize eosinophil function and angiogenic potential under hypoxic conditions. Methods Human peripheral blood eosinophils were cultured in normoxic or hypoxic conditions with or without cytokines. Viability and apoptosis were assessed by Annexin V/PI staining. Anti- or pro-apoptotic protein levels, HIF-1α levels and MAPK phosphorylation were analyzed by immunoblot analysis. Angiogenic mediator release was evaluated by ELISA. Results Hypoxic eosinophils were more viable than normoxic ones after up to three days. In addition in hypoxia, anti-apoptotic Bcl-XL protein levels increased more than pro-apoptotic Bax levels. Hypoxia increased VEGF and IL-8 release. In hypoxic eosinophils high levels of HIF-1α were observed, particularly in the presence of GM-CSF. MAPK, particularly ERK1/2 inhibitors, decreased hypoxia-mediated VEGF release and HIF-1α expression. Conclusion Eosinophils respond to hypoxia by up-regulation of survival and of some of their pro-angiogenic functions indicating a correlation between eosinophilic inflammation and angiogenesis.

Importance: Research has shown evidence of increased substance use (ISU) in populations affected by mass terrorism; however, less is known regarding how psychosocial factors interact to estimate ISU following such events., Objective: To examine which factors are associated with reporting ISU, test whether psychological distress (PD) mediated the association between exposure to trauma and reporting ISU, and whether the mediation effect differed among those with prior mental health (MH) difficulties and those without., Design, Setting, and Participants: A partially representative cross-sectional survey of the adult Jewish population in Israel (aged 18-70 years) was conducted 4 weeks after October 7, 2023 (October 31 to November 5, 2023). A national Web panel using quotas based on national distributions was used. Randomly chosen adult Jewish members were invited to participate until a predetermined sample size was reached., Main Outcomes and Measures: The study measures included reporting ISU (outcome), PD (mediator), exposure to terror events and sociodemographic characteristics (variables), and prior MH difficulties (moderator). Hypotheses regarding outcome and variables were formulated before data collection., Results: A total of 7000 invitations were distributed, 2679 individuals consented, 1432 were excluded owing to quota limits, 74 failed attention tests, and 205 opted out, resulting in 968 participants (490 women [50.6%]; mean [SD] age, 41.5 [14.6] years). Hierarchical regression analysis revealed that participants were significantly more likely to report ISU if they had experienced direct exposure (odds ratio [OR], 5.75; 95% CI, 2.53 to 13.05), indirect exposure (OR, 1.84; 95% CI, 1.27 to 2.67), media exposure (OR, 1.22; 95% CI, 1.09 to 1.36), PD (OR, 1.80; 95% CI, 1.44 to 2.25), or previous MH difficulties (OR, 2.76; 95% CI, 1.86 to 4.09). PD partially mediated the association between indirect exposure (b = 0.20; 95% CI, 0.11 to 0.31) and media exposure (b = 0.14; 95% CI, 0.10 to 0.19) and reporting ISU. No evidence was found to support previous MH difficulties as a moderator of these indirect effects (indirect exposure, b = -0.003; 95% CI, -0.28 to 0.28; media exposure, b = 0.01; 95% CI, -0.06 to 0.08)., Conclusions and Relevance: This study contributes to the research on the association of mass terrorism with ISU while shedding important light on the role it may play in the self-medication of PD following exposure, even in those who might have no previous MH difficulties. These insights are crucial for planning essential health services and preventive measures.

Background: Good technical skills are crucial for surgeons. Yet although surgical training programs strive to assess technical aptitude when selecting surgical residents, valid assessments of such aptitude are still lacking. Surgical simulators have been proposed as a potentially effective tool for this purpose. The current study aims to develop a technical aptitude test using a virtual reality surgical simulator, and to validate its use for the selection of surgical residents., Methods: The study had three phases. In Phase 1, we developed an initial version of the technical aptitude test using the Lap-X-VR laparoscopic simulator. In Phases 2 and 3 we refined the test and collected empirical data to evaluate four main sources of validity evidence (content, response process, internal structure, and relationships with other variables), and to evaluate the feasibility and acceptability of the test. Specifically, Phase 2 comprised a review of the test by 30 senior surgeons, and in Phase 3 a revised version of the test was administered to 152 interns to determine its psychometric properties., Results: Both the surgeons and interns rated the test as highly relevant for selecting surgical residents. Analyses of the data obtained from the trial administration of the test supported the appropriateness of the score calculation process and showed good psychometric properties, including reliability (α = 0.83) and task discrimination (mean discrimination = 0.5, SD = 0.1). The correlations between test scores and background variables revealed significant correlations with gender, surgical simulator experience, and video game experience (ps < 0.001). These variables, however, explained together only 10% of the variance in test scores., Conclusions: We describe the systematic development of an innovative virtual reality test for assessing technical aptitude in candidates for surgical training, and present evidence for its validity, feasibility and acceptability. Further validation is required to support the application of the test for selection, as well as to discern the impact of gender, surgical simulator experience, and video game experience on the fairness of test results. However, the test appears to be a promising tool that may help training programs assess the suitability of candidates for surgical training., (© 2024. The Author(s).)

Background: Otorhinolaryngology / Head and Neck Surgery consists of different sub-specialties, each comprising unique characteristics and challenges. Herein, we investigate the use of a uniform national electronic questionnaire for curriculum planning., Main Outcome Measures: (1) Analyze the residents' perception of the different sub-specialties training programs and their competence capabilities. (2) Identify sub-specialties requiring attention. (3) Investigate the characteristics associated with competence perception., Methods: This is a national cross sectional study. An anonymous electronic questionnaire was emailed to all registered Otorhinolaryngology / Head and Neck Surgery residents., Results: 63.5% registered residents responded to the questionnaire. Two sub-specialties, Rhinology and Laryngology, are located in the extremities of the residents' perceptions of competence and training (p < 0.0001), despite similar complexity perception (means 6.10 and 6.01, respectively). Rhinology is perceived as the most well-trained sub-specialty, both surgically and clinically (means 7.08 and 7.66, respectively), whereas Laryngology is bottom scaled (means 5.16 and 6.14, respectively). The same is true for perceived competence, surgical and clinical, in Rhinology (means 6.80 and 8.02, respectively) compared to Laryngology (means 5.04 and 6.75, respectively). Significant positive correlations were found between training, competence perception and workload ("golden training triangle")., Conclusions: Each ORL-HNS sub-specialty comprises different characteristics and a different learning curve, necessitating a tailored training program. Recognizing its sub-specialties distinctive features may assist in establishment of better-adapted learning curves in residency programs. Herein, we examine the use of anonymous electronic national survey. Laryngology, bottom ranked, is a prototype of a relatively new surgical discipline. Rhinology, ranked top by the residents, is an exemplar of a sub-specialty with an optimal 'educational environment'. Moreover, we have established golden training triangle, implicating, highlights the essential role of institutional and senior staff for proper residency teaching. We demonstrate and advocate the benefit of using an anonymous electronic questionnaire., (© 2023. The Author(s).)

Background: Substance use is a leading cause of preventable morbidity and mortality worldwide. Population-wide screening for problematic substance use in primary health care may mitigate the serious health and socio-economic consequences of such use, but the standard Alcohol, Smoking and Substance Involvement Screening Test (ASSIST 3.1) may be too long for wide-scale screening. How well validated shorter versions (ASSIST-Lite, ASSIST-FC) perform in identifying those with ASSIST 3.1 problematic use in different settings is unclear., Methods: General population Jewish adults in Israel (N = 2,474) responded to an online survey that included the ASSIST 3.1 and sociodemographics. Across substances (alcohol, tobacco, cannabis, sedatives, prescription stimulants, prescription painkillers), receiver operator characteristic curve analysis determined that ASSIST-FC scores performed better than ASSIST-Lite at identifying those with problematic use, and evaluated differential ASSIST-FC performance by gender or age. Test characteristics and agreement were evaluated for binary ASSIST-FC versions, with ASSIST 3.1 problematic use as the gold standard., Results: ASSIST-FC scores showed high ability to identify ASSIST 3.1 problematic use, with minimal differences by gender or age. Binary ASSIST-FC (most substances: threshold 3+; alcohol: 5+) showed high specificity and positive predictive value, acceptable sensitivity, and good agreement., Conclusions: The ASSIST-FC, which assesses frequency of use and other's concerns about use, appears useful for very brief screening in primary care to identify patients who may benefit from intervention. Early identification of those at-risk may prevent more severe consequences and ultimately decrease the significant costs of problematic substance use on the individual and population level., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The efficacy of biological treatment for severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) has recently been demonstrated through double-blinded clinical trials. The aim of this study was to provide preliminary real-world experience regarding biological therapy for uncontrolled CRSwNP. The records of patients who received biological treatment in a tertiary medical center between the years 2019 to 2022 were retrospectively reviewed. Patients included in this study were eligible for biological treatment according to the EPOS 2020 criteria. Among patients who had their first follow-up visit <6 months from the treatment initiation, the Sino-Nasal Outcome Test 22 Questionnaire (SNOT-22) score had decreased by 22% ( p = 0.01) and the nasal polyp score (NPS) had decreased by 48% ( p = 0.05). Among patients who had their first follow-up visit ≥6 months from treatment initiation, the SNOT-22 score had decreased by 40% ( p = 0.03) and the NPS had decreased by 39% ( p = 0.1). The number of patients who needed systemic steroid treatment had decreased by 68% ( p < 0.0001), and the number of patients who needed endoscopic sinus surgery had decreased by 74% ( p < 0.0001). These findings correspond with the improvement of clinical symptoms observed in prior randomized clinical trials, thus showing the effectiveness of biologic medications in the treatment of severe CRSwNP in a real-life setting. Although further cohort studies are warranted, our study also suggests evaluating patients at follow-up visits mainly by quality-of-life aspects and investigating longer dosing intervals of dupilumab.

Background: Temporal bone fractures are divided into otic capsule sparing and otic capsule involving fractures. In the latter, hearing loss, facial nerve paralysis, cerebrospinal fluid leak and meningitis have been reported to occur. The impact of hearing loss can be devastating, especially when occurring in children, with significant risk to speech development and sound localization. In the event of hearing loss, early rehabilitation is therefore of paramount importance. Identification of an intra-operative fracture line with available images and the outcome of such cases has not been reported., Case Presentation: We present the case of a 31-month-old male with an otic capsule involving temporal bone fracture, who presented with ipsilateral profound hearing loss. After all required work-up had been performed, he was admitted for a cochlear implant insertion. Per- operatively, a clear fracture line was seen at the round window niche, but a normal insertion was performed despite the anticipated potential ossification at the fracture line. The dreaded complications of cerebrospinal fluid otorrhea or non-auditory stimulation post-implant did not occur. The peculiarity of this case was its rarity, which was demonstrated by clear images that showed the fracture line on preoperative imaging and intraoperatively., Conclusion: Cochlear implantation in the presence of a visible fracture line is feasible and the surgical procedure must not be aborted at its discovery. In these cases, post-operative bacterial meningitis can occur and should be treated aggressively with systemic antibiotics to avoid contralateral ossification of the labyrinth due to labyrinthitis., (© 2023. The Author(s).)

The aim of the study was to develop a sustained-release varnish (SRV) containing mometasone furoate (MMF) for sinonasal stents (SNS) to reduce mucosa inflammation in the sinonasal cavity. The SNS' segments coated with SRV-MMF or an SRV-placebo were incubated daily in a fresh DMEM at 37 °C for 20 days. The immunosuppressive activity of the collected DMEM supernatants was tested on the ability of mouse RAW 264.7 macrophages to secrete the cytokines' tumor necrosis factor α (TNFα) and interleukin (IL)-10 and IL-6 in response to lipopolysaccharide (LPS). The cytokine levels were determined by respective Enzyme-Linked Immunosorbent Assays (ELISAs). We found that the daily amount of MMF released from the coated SNS was sufficient to significantly inhibit LPS-induced IL-6 and IL-10 secretion from the macrophages up to days 14 and 17, respectively. SRV-MMF had, however, only a mild inhibitory effect on LPS-induced TNFα secretion as compared to the SRV-placebo-coated SNS. In conclusion, the coating of SNS with SRV-MMF provides a sustained delivery of MMF for at least 2 weeks, maintaining a level sufficient for inhibiting pro-inflammatory cytokine release. This technological platform is, therefore, expected to provide anti-inflammatory benefits during the postoperative healing period and may play a significant role in the future treatment of chronic rhinosinusitis.

Background: Mast cells are initiators and main effectors of allergic inflammation, together with eosinophils, with whom they can interact in a physical and soluble cross-talk with marked pro-inflammatory features, the Allergic Effector Unit. The pro-resolution role of mast cells, alone or in co-culture with eosinophils, has not been characterized yet., Objectives: We aimed to investigate select pro-resolution pathways in mast cells in vitro and in vivo in allergic inflammation., Methods: In vitro, we employed human and murine mast cells and analyzed release of resolvin D1 and expression of 15-lipoxygenase after IgE-mediated activation. We performed co-culture of IgE-activated mast cells with peripheral blood eosinophils and investigated 15-lipoxygenase expression and Resolvin D1 release. In vivo, we performed Ovalbumin/Alum and Ovalbumin/S. aureus enterotoxin B allergic peritonitis model in Wild Type mice following a MC "overshoot" protocol., Results: We found that IgE-activated mast cells release significant amounts of resolvin D1 30 min after activation, while 15-lipoxygenase expression remained unchanged. Resolvin D1 release was found to be decreased in IgE-activated mast cells co-cultured with peripheral blood eosinophils for 30 min In vivo, mast cell-overshoot mice exhibited a trend of reduced inflammation, together with increased peritoneal resolvin D1 release., Conclusions: Mast cells can actively contribute to resolution of allergic inflammation by releasing resolvin D1., Competing Interests: Conflict of interests statement The authors have declared that no conflict of interest exists., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Unilateral intratonsillar abscess (ITA) is an underreported, well-known complication of acute tonsillitis. The prevalence of unilateral ITA compared to peritonsillar abscess (PTA) is 1:14. However, bilateral ITA is an extremely rare entity, with only four cases reported thus far., Objectives: To describe past cases and our experience, elaborating the diagnostic challenge and the surgical treatment for bilateral ITA., Methods: We conducted a literature search in the PubMed database using the key words intra-tonsillar abscess, tonsillar abscess, bilateral tonsillar abscess, bilateral intra-tonsillar abscess and bilateral peritonsillar abscess. Our search was limited to the years 1980 to 2020., Results: We found that only four cases of bilateral ITA were previously published. All were characterized by a delay in diagnosis with a median of 10 days (4-14 days), symmetrical oral cavity appearance, enlarged bilateral kissing tonsils, and subsequent treatment by surgical drainage/paracentesis. Respiratory compromise was a concern in most cases. Our patient was treated with bilateral quinsy tonsillectomy and had a prompt recovery., Conclusions: Bilateral ITA is a rare, deceiving entity, with a diagnosis delay attributed to the symmetrical oral bulging. We present the fifth case reported and the first ever reported in a pediatric patient. We describe the assumed pathogenesis and the main characteristics among all five patients, emphasizing the important role of a high index of suspicion and appropriate imaging, guiding to proper diagnosis and treatment.

Allergic rhinitis (AR) is a common rhinopathy that affects up to 30% of the adult population. It is defined as an inflammation of the nasal mucosa, develops in allergic individuals, and is detected mostly by a positive skin-prick test. AR is characterized by a triad of nasal congestion, rhinorrhea, and sneezing. Mast cells (MCs) are innate immune system effector cells that play a pivotal role in innate immunity and modulating adaptive immunity, rendering them as key cells of allergic inflammation and thus of allergic diseases. MCs are typically located in body surfaces exposed to the external environment such as the nasal mucosa. Due to their location in the nasal mucosa, they are in the first line of defense against inhaled substances such as allergens. IgE-dependent activation of MCs in the nasal mucosa following exposure to allergens in a sensitized individual is a cardinal mechanism in the pathophysiology of AR. This review is a comprehensive summary of MCs' involvement in the development of AR symptoms and how classical AR medications, as well as emerging AR therapies, modulate MCs and MC-derived mediators involved in the development of AR.

The aim of the study was to develop a sustained-release varnish (SRV) containing chlorhexidine (CHX) for sinonasal stents (SNS) to reduce bacterial growth and biofilm formation in the sinonasal cavity. Segments of SNS were coated with SRV-CHX or SRV-placebo and exposed daily to bacterial cultures of Staphylococcus aureus subsp. aureus ATCC 25923 or Pseudomonas aeruginosa ATCC HER-1018 (PAO1). Anti-bacterial effects were assessed by disc diffusion assay and planktonic-based activity assay. Biofilm formation on the coated stents was visualized by confocal laser scanning microscopy (CLSM) and high-resolution scanning electron microscopy (HR-SEM). The metabolic activity of the biofilms was determined using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) method. Disc diffusion assay showed that SRV-CHX-coated SNS segments inhibited bacterial growth of S. aureus subsp. aureus ATCC 25923 for 26 days and P. aeruginosa ATCC HER-1018 for 19 days. CHX was released from coated SNS segments in a pH 6 medium up to 30 days, resulting in growth inhibition of S. aureus subsp. aureus ATCC 25923 for 22 days and P. aeruginosa ATCC HER-1018 for 24 days. The MTT assay showed a reduction of biofilm growth on the coated SNS by 69% for S. aureus subsp. aureus ATCC 25923 and 40% for P. aeruginosa ATCC HER-1018 compared to the placebo stent after repeated exposure to planktonic growing bacteria. CLSM and HR-SEM showed a significant reduction of biofilm formation on the SRV-CHX-coated SNS segments. Coating of SNS with SRV-CHX maintains a sustained delivery of CHX, providing an inhibitory effect on the bacterial growth of S. aureus subsp. aureus ATCC 25923 and P. aeruginosa ATCC HER-1018 for approximately 3 weeks.

Background: Nasal polyps are three-dimensional structures arising from the mucosa of the upper airway. Due to their complexity, the reliability of single-layer cell cultures and animal systems as research models is limited., Objectives: To evaluate the feasibility of an ex vivo organ culture of human polyps, preserving tissue structure and function., Methods: Nasal polyps were excised during routine endoscopic sinus surgery for chronic rhinosinusitis and polyposis. Fresh tissue samples were used for pathological evaluation and for the preparation of 250-500 µm sections, which were incubated in culture media. Tissue viability was assessed by visualisation of cilia motility, measurement of glucose uptake, and an infectivity assay. Cytokine secretion was evaluated by enzyme-linked immunosorbent assay and real-time polymerase chain reaction before and after the introduction of steroids., Results: Polyp tissue viability was retained for 2-3 days as demonstrated by cilia motility, glucose uptake and preserved cellular composition. Tissue samples maintained their capacity to respond to infection by herpes simplex virus 1 and adenovirus. Introduction of dexamethasone to cultured tissue samples led to suppression of interferon-g production., Conclusions: The ex vivo nasal polyp organ culture reproduces the physiological, metabolic, and cellular features of nasal polyps. Furthermore, it shows a preserved capacity for viral infection and response to drugs. This system is a useful tool for the investigation nasal-polyps and for the development of novel therapies.

Objectives: To investigate the microbiology profile of infected branchial cleft anomalies compared to deep neck infection and explore the influence of age on culture findings., Study Design: A retrospective case control study., Setting: A single tertiary medical center., Subjects and Methods: Patients treated for branchial cleft anomalies between 2006 and 2016 were included. Demographic data, disease and treatment parameters, and microbiology profile, including bacteria classification, antibiotics resistance patterns, and number of pathogens, were analyzed., Results: Of 278 cases treated for branchial cleft anomalies, we have analyzed 69 cases with infection and pathogen identification. The proportion of monobacterial infections was higher (70.6% vs 44.3%; P = .003; odds ratio [OR], 3.02) and the proportion of Streptococcus species infection was lower (48.9% vs 77.2%; P = .001; OR, 0.282) among the infected branchial cleft cases compared to deep neck infections. Anaerobic bacteria infection did not differ between groups (17.8% and 16.5%, respectively). There was a nonsignificant tendency toward more resistant bacterial strains among the infected branchial clefts (15.6% vs 6.3%; P = .118; OR, 2.726). There was no difference between the bacterial profile of patients younger or older than 16 years., Conclusions: The microbiology profile of infected branchial cleft anomalies is not age related and is different from that of deep neck infections. We demonstrate a relatively high frequency of monobacterial infections, relatively lower streptococcal infection rates, and a substantial contribution by resistant species and anaerobes. Empiric antibiotic treatment should cover Streptococcus species, including penicillin-resistant species, as well as clindamycin-resistant anaerobes.

Background/aim: Head and neck cancer (HNC) patients are usually diagnosed with advanced disease and multimodality therapies are required, as well as prognostic biomarkers to predict their response and assess survival. In this study, we aimed to evaluate the ability and clinical significance of the immune biomarker sIL-2R in HNC patients, to assess therapy response and prognosis., Materials and Methods: We evaluated 328 blood samples from 145 head and neck cancer patients (HNC) from several subgroups: 84 larynx carcinomas pre- and 39 post-therapy, 46 oral cavity carcinomas pre- and 29 post-therapy, 12 nasopharynx carcinomas, 16 parotid and other salivary gland carcinoma patients. The control group included 45 healthy subjects. Serum sIL-2R levels were evaluated by ELISA assays and correlated to disease stage, lymph nodes, response to therapy, survival and cancer differentiation., Results: Significantly higher sIL-2R levels were recorded in all HNC patients, as opposed to controls, in advanced versus early-stage disease that decreased following therapy. sIL-2R distinguished best, in comparison to other tumor markers, between HNC patients and controls. Survival was strongly associated to lower sIL-2R levels in patients entering the study., Conclusion: sIL-2R is a sensitive immune marker for HNC patients. Its levels correlate to disease stage, assess response to therapy and are predictive of recurrence or better survival. We suggest, therefore, using sIL-2R as a reliable prognostic marker in HNC patients as a single marker, or in a combined panel of biomarkers., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Whether the diabetic heart benefits from ischemic preconditioning (IPC), similar to the non-diabetic heart, is a subject of controversy. We recently proposed new roles for iron and ferritin in IPC-protection in Type 1-like streptozotocin-induced diabetic rat heart. Here, we investigated iron homeostasis in Cohen diabetic sensitive rat (CDs) that develop hyperglycemia when fed on a high-sucrose/low-copper diet (HSD), but maintain normoglycemia on regular-diet (RD). Control Cohen-resistant rats (CDr) maintain normoglycemia on either diet. The IPC procedure improved the post-ischemic recovery of normoglycemic hearts (CDr-RD, CDr-HSD and CDs-RD). CDs-HSD hearts failed to show IPC-associated protection. The recovery of these CDs-HSD hearts following I/R (without prior IPC) was better than their RD controls. During IPC ferritin levels increased in normoglycemic hearts, and its level was maintained nearly constant during the subsequent prolonged ischemia, but decayed to its baseline level during the reperfusion phase. In CDs-HSD hearts the baseline levels of ferritin and ferritin-saturation with iron were notably higher than in the controls, and remained unchanged during the entire experiment. This unique and abnormal pattern of post-ischemic recovery of CDs-HSD hearts is associated with marked changes in myocardial iron homeostasis, and suggests that iron and iron-proteins play a causative role/s in the etiology of diabetes-associated cardiovascular disorders.

Background: Endoscopic techniques are an integral part of the neurosurgical armamentarium with a growing list of indications. We describe the purely endoscopic removal of an atypical parasagittal meningioma in a patient who could not undergo standard craniotomy due to severe scalp atrophy following childhood irradiation for tinea capitis., Methods: A 68-year-old man in good general health presented with a parasagittal meningioma that recurred following subtotal removal and adjuvant fractionated stereotactic radiosurgery (FSR). The scalp above the tumor location was very diseased and precluded a regular craniotomy for tumor removal. A 4-cm craniotomy was made in the midline forehead, where the skin was normal. A rigid endoscope was advanced under neuronavigation through the interhemispheric fissure, which provided good access with limited retraction, until the tumor was encountered at a depth of 7-8 cm. Two surgeons performed the surgery using a "four-hands technique". The tumor was removed and the insertion area was resected and coagulated., Results: The surgery was uneventful, with no coagulation or transection of major veins. A subtotal resection was achieved, and the patient recovered with no neurological deficit., Conclusions: Safe resection of parasagittal meningiomas with a purely endoscopic technique is feasible. This option needs further exploration as an alternative strategy in patients with severely atrophic scalp skin that greatly increases the risk of significant healing complications with calvarian craniotomy.

Head and neck cancer patients treated by radiation commonly suffer from a devastating side effect known as dry-mouth syndrome, which results from the irreversible loss of salivary gland function via mechanisms that are not completely understood. In this study, we used a mouse model of radiation-induced salivary hypofunction to investigate the outcomes of DNA damage in the head and neck region. We demonstrate that the loss of salivary function was closely accompanied by cellular senescence, as evidenced by a persistent DNA damage response (γH2AX and 53BP1) and the expression of senescence-associated markers (SA-βgal, p19ARF, and DcR2) and secretory phenotype (SASP) factors (PAI-1 and IL6). Notably, profound apoptosis or necrosis was not observed in irradiated regions. Signs of cellular senescence were also apparent in irradiated salivary glands surgically resected from human patients who underwent radiotherapy. Importantly, using IL6 knockout mice, we found that sustained expression of IL6 in the salivary gland long after initiation of radiation-induced DNA damage was required for both senescence and hypofunction. Additionally, we demonstrate that IL6 pretreatment prevented both senescence and salivary gland hypofunction via a mechanism involving enhanced DNA damage repair. Collectively, these results indicate that cellular senescence is a fundamental mechanism driving radiation-induced damage in the salivary gland and suggest that IL6 pretreatment may represent a promising therapeutic strategy to preserve salivary gland function in head and neck cancer patients undergoing radiotherapy., (©2016 American Association for Cancer Research.)

Background/aim: Establishing prognostic factors is very important in the management of cancer patients. Our aim was to evaluate the clinical significance of a panel of tumor markers, including CEA (Carcino Embryonic Antigen), SCC (Squamous Cell Carcinoma Antigen), TPS (Tissue Polypeptide Specific Antigen) and CYFRA 21-1 in head and neck cancer patients, for assessing treatment response and prognosis of patients., Patients and Methods: We evaluated 312 blood samples from 143 head and neck cancer patients, from several sub-groups: 82 Larynx Carcinoma pre- and 38 post-therapy, 46 Oral Cavity pre and 29 post-therapy, 12 nasopharynx, 16 parotid and other salivary gland patients. Blood tumor markers levels were evaluated by conventional ELISA assays. Correlations of marker levels to stage of disease, lymph node involvement and therapy, were performed., Results: Serum levels of all four tumor markers were higher before therapy and decreased thereafter in all patients. The decrease in TPS level following therapy was significant (p=0.03). Significantly higher levels of TPS and similarly higher levels of the other tumor markers were demonstrated in advanced disease (stages III and IV) patients, as opposed to early disease (stages I and II) patients (p=0.012). Node positive patients had significantly higher TPS levels as compared to node negative (p=0.02). The same trend was shown by the other markers as well, but did not reach statistical significance. TPS was best correlated to survival of patients; those having low levels had the best clinical outcome and longer survival., Conclusion: CEA, SCC, TPS and CYFRA 21-1 can all serve as useful tumor markers in HNC patients. They assessed response to therapy and were prognostic for recurrence. TPS proved to be the most sensitive predictor of advanced disease and poor prognosis., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Redox-active iron, a catalyst in the production of hydroxyl radicals via the Fenton reaction, is one of the key participants in ROS-induced tissue injury and general inflammation. According to our recent findings, an excess of tissue iron is involved in several airway-related pathologies such as nasal polyposis and asthma., Objective: To examine the anti-inflammatory properties of a newly developed specific iron-chelating complex, Zn/Ga-DFO, in a mouse model of asthma., Materials and Methods: Asthma was induced in BALBc mice by ovalbumin, using aluminum hydroxide as an adjuvant. Mice were divided into four groups: (i) control, (ii) asthmatic and sham-treated, (iii) asthmatic treated with Zn/Ga-DFO [intra-peritoneally (i/p) and intra-nasally (i/n)], and (iv) asthmatic treated with Zn/Ga-DFO, i/n only. Lung histology and cytology were examined. Biochemical analysis of pulmonary levels of ferritin and iron-saturated ferritin was conducted., Results: The amount of neutrophils and eosinophils in bronchoalveolar lavage fluid, goblet cell hyperplasia, mucus secretion, and peri-bronchial edema, showed markedly better values in both asthmatic-treated groups compared to the asthmatic non-treated group. The non-treated asthmatic group showed elevated ferritin levels, while in the two treated groups it returned to baseline levels. Interestingly, i/n-treatment demonstrated a more profound effect alone than in a combination with i/p injections., Conclusion: In this mouse model of allergic asthma, Zn/Ga-DFO attenuated allergic airway inflammation. The beneficial effects of treatment were in accord with iron overload abatement in asthmatic lungs by Zn/Ga-DFO. The findings in both cellular and tissue levels supported the existence of a significant anti-inflammatory effect of Zn/Ga-DFO.

Cardiovascular dysfunction is a major complication of diabetes. Examining mechanistic aspects underlying the incapacity of the diabetic heart to respond to ischemic preconditioning (IPC), we could show that the alterations in iron homeostasis can explain this phenomenon. Correlating the hemodynamic parameters with levels of ferritin, the main iron storage and detoxifying protein, without and with inhibitors of protein degradation, substantiated this explanation. Diabetic hearts were less sensitive to ischemia-reperfusion stress, as indicated by functional parameters and histology. Mechanistically, since ferritin has been shown to provide cellular protection against insults, including ischemia-reperfusion stress and as the basal ferritin level in diabetic heart was 2-fold higher than in controls, these are in accord with the greater resistance of the diabetic heart to ischemia-reperfusion. Additionally, during ischemia-reperfusion, preceded by IPC, a rapid and extensive loss in ferritin levels, during the prolonged ischemia, in diabetic heart but not in non-diabetic controls, provide additional substantiation to the explanation for loss of respond to IPC. Current research is shedding light on the mechanism behind ferritin degradation as well, suggesting a novel explanation for diabetes-induced loss of cardioprotection.

Organ-specific changes of iron- and redox-related proteins occur with age in the rat. Ferritin, the major iron storage and detoxifying protein, as well as the proteins of the methionine-centered redox cycle (MCRC) were examined in old and young animals, and showed organ-dependent changes. In spleens and livers of aged rats, ferritin (protein) levels were greater than in young ones, and their iron saturation increased, rendering higher ferritin-bound iron (FtBI). Iron saturation of the ferritin molecule in the tongues and sternohyoids of old rats was lower but ferritin level was higher than in young rats, resulting in increased FtBI with age. Ferritin level in the esophagus of older rats was lower than in young rats but its molecular iron content higher thus the total FtBI remained the same. In the larynx, both ferritin and its iron content were the same in young and old animals. MCRC proteins were measured in livers and spleens only. With aging, methionine sulfoxide reductase A and B (MsrA and MsrB) levels in livers and spleens decreased. Thioredoxin1 (Trx) and Trx-reductase1 were elevated in old spleens, but reduced in livers. Aged spleens showed reduced Msr isozyme activity; but in the liver, its activity increased. mRNA changes with age were monitored and found to be organ specific. These organ-specific changes could reflect the different challenges and the selective pathways of each organ and its resultant capacity to cope with aging.

Histamine is a key mediator of allergic inflammation, primarily through competitive antagonism of binding to H1 receptors. In this issue, Weller and Maurer report that the H1 antagonist desloratadine possesses mast cell-stabilizing properties when challenged in an IgE-dependent or -independent fashion. Thus, desloratadine provides benefits that are independent of H1 receptor binding and based on mast cell stabilization.

Allergic, inflammatory, and immune responses carried out by eosinophils are regulated by the cross talk between activatory and inhibitory signals. While much data has been obtained on activatory signals, inhibitory receptors on these cells have received scant attention. Therefore, we screened the surface of human peripheral blood eosinophils for inhibitory receptors using monoclonal antibodies (mAbs) previously generated to recognize receptors on human natural killer cells. Eosinophils from all of the donors examined expressed the inhibitory receptors IRp60, LIR3/ILT5, FcgammaRIIB, and p75/AIRM but not LIR1/ILT2, p58.1, p58.2, p70, or NKG2A/CD94 (n = 15). Interestingly, 25% of the donors expressed p140. IRp60 cross-linking inhibited eotaxin-dependent transmigration of eosinophils in a calcium-independent fashion. In addition, cross-linking of IRp60 on the eosinophils in the presence of IL-5/GM-CSF inhibited the antiapoptotic effect of these cytokines and blocked the release of TNF-alpha, IL-1beta, IFN-gamma, IL-4, and 3T3 fibroblast proliferation. Cross-linking of IRp60 inhibited IL-5-mediated JAK2 phosphorylation as well as eotaxin- and IL-5/GM-CSF-mediated ERK1/2 and p38 phosphorylation. Furthermore, upon cross-linking, IRp60 underwent tyrosine phosphorylation and recruited SHP-1 but not SHP-2. These findings demonstrate a novel pathway for suppressing the activity of human eosinophils, thus indicating IRp60 as a future potential target for the treatment of allergic and eosinophil-associated diseases.